FHL2 基因变异致扩张型心肌病 1 例并文献回顾

Objective To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM). MethodsClinical data of the child who had presented at Zhengzhou Children′s Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES)was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. "FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features. ResultsThe patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c. 391C>T (p.Arg131Cys) in FHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of ten patients with FHL2 gene variants have been reported by previous literature, six of them presented with DCM, two with hypertrophic cardiomyopathy (HCM), and two with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c. 391C>T (p.Arg131Cys) has been identified in a child with DCM, though this variant has not been validated among the patient′s family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c. 391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+ PM2_Supporting+ PP3+ PP5). ConclusionThe heterozygous missense variant of c. 391C>T (p.Arg131Cys) in the FHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of trio-WES in the clinical diagnosis and genetic counseling.